Medical and Minimally Invasive Treatment of Urinary Incontinence

Treatment Update

TREATMENT UPDATE Medical and Minimally Invasive Treatment of Urinary Incontinence John P. Lavelle, MB, BCh, FRCSI* Seamus Teahan MB, BCh, FRCSI† Duk-Yoon Kim, MD Michael B. Chancellor, MD *Division of Urologic Surgery University of Pittsburgh School of Medicine Pittsburgh Beaumont Hospital Dublin, Ireland † Newer agents and procedures give urologists more options in treating patients who have urinary incontinence related to such etiologies as an ineffective sphincter, detrusor hypersensitivity, obstruction, or a combination of these. Abolition of the involuntary contractions characteristic of detrusor instability can be accomplished pharmacologically or surgically. First-line anticholinergic agents are tolterodine and oxybutynin XL, given orally. Alternatively, intravesical administration provides a high concentration of drug, such as capsaicin or resiniferatoxin, at the detrusor muscle level. However, this commits the patient to intermittent self-catheterization. Surgery is reserved for those who have failed prolonged trials of conservative therapies. For patients with intractable urge incontinence, urologists have the new technique of sacral nerve stimulation. [Rev Urol 1(2):111-120, 1999] Key Words: Bladder • Urethra • Urodynamics • Incontinence, urinary • Bladder, neurogenic T he management of incontinence depends on the etiology, which includes: (1) an ineffective sphincter, leading to stress incontinence; (2) detrusor hypersensitivity, with resulting urgency or urge incontinence; or (3) obstruction, with possible overflow incontinence. The focus of this article is management of urgency and urge incontinence caused by the overactive bladder in neurologically normal individuals or detrusor hyperreflexia in those with a neurologic lesion. In addition to the current armamentarium available to urologists, the latest management options for the overactive bladder will be reviewed. These include 2 new medications, tolterodine and oxybutynin XL, and a novel approach using intravesical capsaicin or resiniferatoxin. Also available for treating patients with incontinence who are refractory to treatment is the minimally invasive technique of sacral nerve stimulation. SPRING 1999 REVIEWS IN UROLOGY 111 Mixed Incontinence Evaluation of Incontinence Evaluation of a patient with urge and stress incontinence should be done with a formal history, voiding diary, and urodynamic evaluation. This is as important postoperatively as preoperatively. The postoperative evaluation seeks to rule out outlet obstruction or denervation of the bladder leading to the detrusor instability. Infection, bladder tumors, carcinoma in situ, bladder stones, and interstitial cystitis are unlikely causes of instability in the postoperative situation—with the possible exception of infection. Indeed, a preoperative evaluation should have excluded these causes. However, a full differential evaluation is warranted if the patient is pre- senting late from the time of operation with symptoms suggestive of bladder instability. A voiding diary is a useful tool to help correlate the amount and frequency of micturition with the patient’s symptoms. In the preoperative evaluation of patients with stress incontinence, the finding of detrusor instability does not exclude the repair of the cause of stress incontinence and treatment of the patient with detrusor instability afterward. The ramifications have to be made clear to the patient—that detrusor instability may lead to an incomplete cure of symptoms, but that the symptoms may be manageable with medication or other means. This does not mean that urologists Physiology and Definition of Terms Physiology. The primary functions of the bladder and lower urinary tract are the storage and timely expulsion of urine, plus maintenance of a barrier between urine and plasma. The bladder is capable of accomplishing its storage function by painlessly accepting large volumes of urine with little or no change in intravesical pressure. Continence is maintained by the sphincters of the bladder neck (internal sphincter) and the striated muscle of the urethral sphincter (external sphincter). Micturition is a finely tuned, coordinated event characterized by opening of the sphincters and detrusor muscle contraction. According to the International Continence Society (ICS): “The unstable detrusor is one that is shown objectively to contract, spontaneously or on provocation, during the filling phase while the patient is attempting to inhibit micturition.”20,21 In 1 report, approximately 50% of patients were able to voluntarily abort involuntary bladder contractions when asked to do so during a urodynamic study.22 Therefore, if during cystometry patients are instructed to abort micturition, as per the recommendations of the ICS, up to 50% of patients with detrusor instability will remain undetected. Our recommendation is that patients should report sensations to the examiner during a urodynamic study without necessarily trying to inhibit micturition. If the bladder spontaneously contracts during filling in this setting, the detrusor is unstable. From a clinical perspective, the etiology of detrusor overactivity has been attributed to a variety of causes (Table 1). In certain neurologic disorders, the cause and effect relationship is obvious and well studied. In others, such as inflammation and infection, the relationship is mere conjecture. Other etiologies for detrusor instability include urethral and bladder trauma, bladder outlet obstruction, aging, and anxiety neurosis.8 Due to incomplete understanding of the pathophysiology of the unstable bladder, attempts to improve the management of this condition are difficult.23 Definition of Terms. The generic term for involuntary detrusor contractions is detrusor overactivity (ICS classification). When involuntary detrusor contractions are caused by neurologic pathology, the condition is called detrusor hyperreflexia. In the absence of a neurologic lesion, the condition is termed detrusor instability. When there is insufficient clinical information to make this distinction, such as in the frail elderly, the generic term detrusor overactivity is preferred. 112 REVIEWS IN UROLOGY SPRING 1999 should manage unstable bladders with surgical repair; rather, they should manage both conditions independently and concurrently. Patients with defined stress and urge incontinence require a clear understanding of both problems to allow adequate treatment. There are a few caveats when considering treatment strategies for female patients: • Women with clearly defined stress incontinence, who void frequently to avoid symptoms. These patients will respond well to surgery. Urodynamic evaluation will show a stable bladder.1 • Women with no symptoms of frequency, urgency, or urge incontinence with sphincteric incontinence but found to have an unstable detrusor on cystometrogram. Such patients may be treated safely for stress incontinence. The urodynamic findings should be documented and discussed with the patient. • Women with both sphincteric incontinence and detrusor instability. Patients with these conditions should be treated initially with anticholinergic medication for urgency symptoms. If the patient does not respond completely, surgery is appropriate. The patient should be told, however, that in up to 75% of patients, the urge incontinence will resolve or significantly diminish after surgery. She should also be told there is up to a 15% chance that the overactive bladder may be worsened.2 The only accurate means of confirming a diagnosis of bladder outlet obstruction is by video/pressure/flow urodynamic studies; an impaired flow rate alone is insufficient for diagnosis, since diminished flow is more commonly caused by impaired detrusor contractility than bladder outlet obstruction.3 The sine qua non for the diagnosis is the presence of a detrusor contraction of adequate magnitude and duration and an impaired flow rate. Although precise data on normal flow rates are lacking at present, it Mixed Incontinence seems reasonable to consider a maximum flow rate of <12 mL/sec with a voided volume of 200 mL or more associated with a maximum voiding pressure of >30 cm H2O to be indicative of obstruction in a woman.4 Nevertheless, since symptomatic detrusor instability usually subsides after relief of obstruction in men, it is worth excluding obstruction by performing a screening uroflow study. Table 1 Possible Etiology of the Unstable Bladder Condition Examples Bladder outlet obstruction More common in males BPH, urethral stricture Neurologic disease Multiple sclerosis, stroke, spinal cord injury, parkinsonism, diabetes mellitus, detrusor sphincter dyssynergia Irradiation and chemical cystitis Following irradiation of pelvic tumors of prostate, rectum, and cervix Treatment of Detrusor Instability The principle of treatment of urinary incontinence due to detrusor instability is abolition of involuntary contractions (Fig. 1). This may be accomplished pharmacologically or surgically. Over the past decade, a number of other therapies have been advocated including behavior modification, electrical stimulation, and biofeedback (Table 2). Pharmacologic Therapy. Current research is exploring different pharmacologic agents that may affect the detrusor muscle more than other muscles of the body. The main problem is that the precise sensory pathway of the bladder is poorly understood. Thus, how to alter the sense of urgency, or sensation of bladder fullness, is only empirically known and treated. There is evidence that there are multiple different subtypes of muscarinic and serotonin receptors in the detrusor. There is also evidence that nitric oxide and adenosine triphosphate may also play a significant role in the sensory pathway of the bladder. Again, the mechanism is poorly understood. With time, the mechanisms will be elucidated, and newer pharmacologic agents for managing detrusor instability will likely become available. Oral Therapy. Anticholinergics are competitive inhibitors of acetylcholine that block its muscarinic effects. All of the active drugs must be given in an adequate dosage to ensure a physiologic effect. In practice, the dosage may be increased every 3 to 5 Bladder neoplasm and carcinoma in situ Infection Bacterial, viral, and schistosomiasis Anatomic defects Urethral hypermobility and deficiency, cystocele, uterine prolapse, pregnancy Idiopathic Interstitial cystitis Psychogenic Neurotransmitter imbalance Depression, psychiatric patients on treatment days until the patient improves clinically or until untoward side effects, such as dry mouth, blurred vision, or supraventricular tachycardia, occur (Table 3). Anticholinergic agents are contraindicated in patients with untreated closed-angle glaucoma. First-line anticholinergics. For the first time since the approval of oxybutynin in 1972, new medications have become available for treating the patient with an overactive bladder. With the recent approval of tolterodine (Detrol®) and oxybutynin XL (Ditropan®), what were previously considered first- and second-line Table 2 Treatment of Detrusor Instability Pharmacologic Oral Intravesical Tolterodine Oxybutynin Tricyclic antidepressants Capsaicin Resiniferatoxin Electrical stimulation Sacral nerve stimulation Surgery Urethrolysis Augmentation cystoplasty Behavior modification SPRING 1999 REVIEWS IN UROLOGY 113 Mixed Incontinence continued Infection, inflammation, pelvic floor dysfunction Voluntary Control Treatment Involuntary Reflex Mechanisms Neurological diseases Aging, idiopathic Figure 1. The micturition reflex is typically under voluntary control. A variety of neurologic diseases, aging, bladder outlet obstruction, pelvic floor prolapse, and inflammation can cause the micturition reflex to become overactive. mouth was reported in 6% of patients taking placebo, 4% of those taking 1 mg tolterodine, 17% of of those taking 2 mg tolterodine, and 60% of those receiving oxybutynin.5 Dry mouth is much less of a problem for patients taking tolterodine. The usual dosing is 2 mg bid.6 A recent double-blind, randomized, placebo-controlled, parallel-group, multicenter study had 90 patients with detrusor hyperreflexia and symptoms of urinary urgency, frequency, and/or urge incontinence.7 Urodynamic variables, micturition diary variables, and subjective urinary symptoms were measured before and after 2 weeks’ medications for the overactive bladder need to be revised. State of the art in 1999 is tolterodine and oxybutynin XL as first-line therapy. Everything else is a second-line choice. Tolterodine, an antimuscarinic drug, is just as effective as oxybutynin in reducing urgency and detrusor instability and is much better tolerated than oxybutynin because of its decreased salivary gland activity. Traditionally, up to about 43% of patients receiving oxybutynin would terminate therapy due to problems with dry mouth. In a meta-analysis of 4 multicenter prospective trials of 1120 patients, moderate to severe dry Table 3 Pharmaceuticals for Overactive Bladder Drug Dosage Dicyclomine hydrochloride Flavoxate hydrochloride Hyoscyamine sulfate Imipramine hydrochloride Oxybutynin chloride Controlled-release oxybutynin Propantheline bromide Tolterodine 20 mg tid 100-200 mg tid-qid 0.125 mg tid-qid 10-50 mg bid 2.5-5.0 mg tid 5-20 mg qd 15-30 mg tid-qid 1-2 mg bid Side effectis: + = mild, ++++ = severe. 114 REVIEWS IN UROLOGY SPRING 1999 Anticholinergic side effects +++ + ++ +++ ++++ + ++++ + treatment with either placebo or tolterodine 0.5, 1, 2, or 4 mg twice daily. Linear regression analysis showed a significant dose-response relationship for several clinically relevant urodynamic variables and subjective assessment of symptoms with increasing dosages of tolterodine. There were no safety or tolerability concerns regarding any of the dosages of tolterodine investigated, although 2 patients treated with a dosage of 4 mg bid experienced urinary retention that necessitated dosage reduction. The results of this study suggested that tolterodine is well-tolerated and exerts a dose-dependent effect on bladder function in patients with overactive bladder. Oxybutynin chloride and propantheline bromide (Pro-Banthine®) were the 2 most widely used agents for detrusor overactivity until tolterodine was released. While detrusor overactivity is not listed as an indication, subjective improvement has been reported in 50% to 80% of patients whose detrusor instability was treated with oxybutynin. However, objective urodynamic improvement occurs in only 40%. In a double-blind, placebo-controlled, randomized crossover trial comparing oxybutynin with placebo in 53 women, oxybutynin was associated with a significantly greater improvement than placebo at the first desire to void and cystometric capacity.8 Oxybutynin is usually started at 5 mg tid, and it is rarely necessary to exceed the 15 mg daily dose. Oxybutynin, in a once-a-day controlled release formulation, has just obtained FDA approval and will be available in early 1999. Both the long- and short-acting formulations show comparable efficacy and effectiveness. In a study of 105 patients in a multicenter, prospective, randomized, placebo-controlled trial, patients taking the long-acting preparation reported significantly fewer problems with moderate or severe dry mouth (24.5% vs 46.2%).9 Mixed Incontinence continued Main Points √ Video/pressure/flow urodynamic studies can confirm a diagnosis of bladder outlet obstruction. A maximum flow rate of <12 mL/sec with a voided volume of 200 mL or more with a maximum voided pressure of >30 cm H2O indicates obstruction in a woman. √ First-line oral anticholinergic agents for patients with overactive bladders are tolterodine and oxybutynin XL. √ A new agent is duloxetine, which appears to reduce bladder overactivity. The drug inhibits 5-HT3 and norepinephrine reuptake. √ Intravesical instillation of capsaicin or resiniferatoxin offers the option of obtaining a high concentration of drug at the level of the detrusor muscle. √ With a minimally invasive, nondestructive surgical technique, sacral nerve stimulation, urologists can implant electrodes and a pacemaker unit to inhibit sensory processing in the spinal cord in patients with intractable urge incontinence. Second-line anticholinergics. Propantheline is usually started at 15 mg qid. Dosages as high as 120 mg/d are sometimes needed, because of the erratic absorption of the drug. This is regarded as a second-line anticholinergic, since the effects of propantheline on the smooth muscle of the bladder are different from other antimuscarinic agents. Dicyclomine hydrochloride (Bentyl®) possesses a direct relaxant effect on smooth muscle in addition to an antimuscarinic action. An oral dose reflexia in a elderly population.10 Chapple and associates reported in 1990 on a double-blind, placebocontrolled, crossover trial of flavoxate in idiopathic detrusor instability.11 The results revealed no advantage of flavoxate over placebo. Alternative Medications for the Overactive Bladder. Duloxetine is a 5HT3 and norepinephrine reuptake inhibitor. This new agent appears to have little effect on the normal bladder. However, in animal studies of chemically irritated bladders, these Intravesical administration of drugs . . . offers the possiblity of obtaining a high concentration of drug at the detrusor muscle level and avoids systemic side effects. of 20 mg tid has been reported to increase bladder capacity in patients with detrusor hyperreflexia, although this is not listed as an indication for this drug. Flavoxate hydrochloride (Urispas®) is another compound that has been reported to have a direct inhibitory action on smooth muscle in addition to anticholinergic and local analgesic properties. The recommended dose is 100 to 200 mg tid or qid. Although clinical improvement has been reported in patients with unstable bladders, Briggs et al reported in 1980 no effect on detrusor hyper- 116 REVIEWS IN UROLOGY SPRING 1999 agents appear to reduce the overactivity of the bladder. The mechanisms may be via the 5-HT3 receptor and the α1-andrenergic mechanisms.12 Tricyclic antidepressants’ exact mode of action have not been demonstrated clearly, but they exert anticholinergic and sympathomimetic actions in addition to a central effect. For the unstable bladder, imipramine (Tofranil®) is the most commonly used tricyclic antidepressant. The usual starting dosage is 25 mg qd. Unlike the anticholinergics, a blood level of imipramine builds up over several weeks. The effect of imipramine may not be apparent for at least that period. The dose is increased weekly by 25 mg until the patient is clinically well or has anticholinergic side effects. However, if the drug must be discontinued, it should be tapered over several weeks lest a severe rebound depression occur. In our experience, the effects of imipramine on the bladder and urethra are often additive to those of anticholinergic agents. Consequently, a combination of imipramine and oxybutynin is sometimes especially useful. The use of tricyclic antidepressants for the overactive bladder should only be in patients who are carefully evaluated according to the AHCPR 1996 guidelines.13 There are no published data on the use of tricyclic antidepressants with the newer agents tolterodine, capsaicin, or resiniferatoxin. Other pharmacological approaches have been described, including prostaglandin inhibitors, scopolamine, baclofen, and bromocriptine with variable success.14 Cardozo and Stanton reported symptomatic improvement in patients with detrusor instability given indomethacin; however, this was a short-term study without urodynamic results.15 Cornella and associates demonstrated a 30% subjective improvement in detrusor instability symptoms with scopolamine, but 70% of the patients experienced moderate to severe side effects16 leading to discontinuation of medication. Intravesical Therapy. Intravesical administration of drugs has been tried as an alternative to conventional oral agents for the unstable bladder. This route of instillation offers the possibility of obtaining a high concentration of drug at the detrusor muscle level and avoids systemic side effects. Our own experience with intravesical instillation of anticholinergic agents has been partially successful. The technique is awkward, and the patient needs to learn inter- Mixed Incontinence mittent self-catheterization. This route of administration may be of value to patients who are already committed to intermittent selfcatheterization. Capsaicin, a substance P antagonist, has been tried recently with limited success. The primary problem with capsaicin is that the drug causes severe discomfort or pain initially due to maximal release (excitation) of substance P or neurokinin A by neurons in the bladder, principally the unmyelinated C fibers and myelinated A delta fibers. The use of this substance is still largely experimental, primarily for patients with detrusor hyperreflexia. Some trials are ongoing using capsaicin for detrusor instability, especially in patients who have failed other forms of treatment. In a recent study of patients with Table 4 Capsaicin Clinical Results25 Number of series Number of patients Symptomatic improvement Capacity pre (mL) Capacity after (mL) Maximum effect duration key advantage of RTX is that it is at least as effective as capsaicin but without the burning side effect. Other intravesical agents. In properly motivated patients or patients who cannot tolerate oral anticholinergic agents, intravesical instillation should be considered as a nonsurgical option. Agents studied thus far include emepronium bromide, intravesical lidocaine, oxybutynin, The principles behind SNS can be summarized as somatic afferent inhibition of sensory processing in the spinal cord. detrusor hyperreflexia, 44% of patients had satisfactory continence, 36% showed improvement, and only 20% failed treatment (Table 4).17 Resiniferatoxin [RTX] is a much more potent sensory antagonist than capsaicin and shares a similar homovanilloid receptor to capsaicin without the excitatory effect of capsaicin. This is showing promising potential for use in bladder instability and detrusor hyperreflexia to reduce spasms without the discomfort of capsaicin. However, formal controlled trials still have to be performed to determine the precise use and dosage regimen for this agent. Initial results in a human trial revealed that 1 month after a single instillation of resiniferatoxin, 25% of the patients maintained an increased bladder volume with decreased symptoms, and that all the patients had increased bladder capacity immediately after instillation.18 The and verapamil. These all have shown varying degrees of success. Oxybutynin, in fact, may be tolerated better intravesically—with plasma levels comparable to oral administration—while producing less dry mouth problems. Minimally Invasive Procedures for Detrusor Overactivity Surgery is only indicated occasionally in patients with refractory detrusor instability. Older therapies such as denervation, myomectomy, diversion, and rhizotomy are generally no longer considered, except in exceptional circumstances. Hydrodistention may be of use in differentiating interstitial cystitis. Only women who have failed prolonged trials of more conservative therapies should be considered for surgery (Table 5). Almost all surgical therapies are designed, in one way or another, to 6 131 72% (40%-100%) 144 (72-195) 267 (185-321) (1 month-5 years) circumvent the problems. None of the procedures purports to abolish detrusor instability and restore normal micturition. When detrusor instability is “abolished” by surgical intervention, detrusor contractility is also adversely altered, and subsequent bladder emptying generally requires abdominal straining or intermittent self-catheterization. Although abdominal straining appears easier and less invasive, with prolonged straining, a significant number of patients develop day and nighttime urinary frequency and stress incontinence. For this reason, we recommend intermittent self-catheterization. We always discuss with patients the likelihood of detrusor areflexia and the need for permanent intermittent self-catheterization before asking for their consent to a surgical procedure. For female paraplegics or those women unable to perform selfcatheterization through the urethra because of physical limitations, continent urinary diversion or augmentation cystoplasty with a continent Table 5 Surgical Treatment of Urge Incontinence Hydrodistention Denervation Transvaginal Ingelmann-Sundberg Phenol, ethanol injection Myomectomy Enterocystoplasty Repair of stress incontinence/prolapse Sacral nerve stimulation SPRING 1999 REVIEWS IN UROLOGY 117 Mixed Incontinence continued b a Figure 2. With one end of the lead in place through the S3 foramen (a), the other end is tunneled to a flank opening. The pulse generator is inserted in an abdominal pocket (b), and its lead tunneled to connect at the flank opening. abdominal stoma is preferred. Sacral Nerve Stimulation. Until the approval of sacral nerve stimulation [SNS], urologists had little to offer if a patient with urge incontinence failed conventional treatment of anticholinergic drugs and behavioral or biofeedback. There simply was not any good surgical treatment. Intestinal bladder augmentation may “cure” the urge incontinence, but this is major surgery with an irreversible change of lifestyle that few nonneuropathic patients are willing to accept. What other surgical options are available? Subtrigonal phenol injection and a denervation procedure have been described, but success rates are not high, and there is little enthusiasm in the urologic community for these procedures. SNS (Interstim, Medtronic, Inc, Minneapolis), is a minimally invasive, nondestructive new surgical technique developed by urologists for urologists. Just as collagen injection for stress incontinence doesn’t burn your bridges for other, more invasive treatment options if it does not work, if SNS is not successful, it causes no Brain Bladder Afferent (+) (-) Bladder (+) (-) Parasympathetic Smooth muscle SNS (+) (+) (-) Parasympathetic External sphincter Figure 3. Sacral nerve stimulation can inhibit sensory processing in the spinal cord. 118 REVIEWS IN UROLOGY SPRING 1999 permanent damage and does not preclude the patient or urologist from any other mode of therapy. This method should be reserved for the patient with intractable urgency and urge incontinence who has failed other methods of treatment. The treatment itself consists of a trial implant with a temporary stimulation unit. If successful, the next step is a permanent implant. The electrodes for SNS are usually placed on an outpatient basis through the S3 sacral foramen. These are then attached to a TENS unit-like pulse generator and stimulated appropriately. The trial period lasts for a week; if results are successful, a permanent pacemaker unit is placed on the electrode for permanent stimulation (Fig. 2). The parameters of stimulation are modulated by noninvasively changing the pacemaker parameters. The principles behind SNS can be summarized as somatic afferent inhibition of sensory processing in the spinal cord (Fig. 3). Pudendal afferent input can also turn on voiding reflexes by suppression of the guarding reflexes. Pudendal afferent input to the sacral spinal cord inhibits supraspinally mediated hyperactive voiding by blocking ascending sensory mechanisms. In a recent study, Mixed Incontinence use of SNS reduced the number of incontinence episodes and pads that were used per day (Fig. 4).19 It is not difficult to implant SNS. Urologists have all the skills and background to perform this procedure with proper training. A focus course and hands-on mentoring are recommended for the first few cases. Having been mentors of SNS for more than 18 months, we believe SNS belongs in the hands of urologists. Augmentation Cystoplasty. Historically, augmentation cystoplasty was the only surgical option for urgency and urge incontinence. This is a drastic destructive measure in which the dome of the bladder is replaced with an intestinal segment. This commits the patient permanently to clean, intermittent catheterization for urinary drainage. This procedure is now only reserved for complete failure of all other modalities of treatment and willingness of the patient to perform clean, intermittent catheterization permanently. Behavior Modification. Behavior modification is an effective way to manage the symptoms of detrusor instability, because it “teaches” the patient to regain control of the blad- der and sphincter. There is an intensive bladder retraining program, which requires considerable expense of time, effort, and dedication on the part of the patient and the therapist. Some of the principles are quite simple. For example, the patient maintains a weekly voiding diary. Fluid restriction is recommended to decrease urine output and, therefore, reduce urinary incontinence. In addition, the patient is taught muscle contracting techniques such as the Kegel exercises, which are designed to abort involuntary detrusor contractions. When there is associated bladder pain and stress, stress relaxation techniques are also utilized. Behavior modification can be useful in male patients with stress incontinence with urgency after a radical prostatectomy. For the reasons outlined above, stress incontinence due to sphincter damage resulting from surgery may be worsened from detrusor instability secondary to the stress incontinence. If a program of Kegel’s exercises improves the stress incontinence, urgency should also decrease, leading to a more satisfactory result for the patient. The technique may also be combined with pharma- Sacral Nerve Stimulation 10 Baseline 9 6-month 8 n=34 7 6 5 4 3 2 1 0 Incontinence episodes/day Pads/day Figure 4. The number of urge incontinence episodes and pads used per day significantly decreased 6 months after sacral nerve stimulation.19 cotherapy to reduce urgency. This technique will only work if the patient is persistent with the exercises and also has a urodynamic evaluation demonstrating that he is capable of physically closing the urinary sphincter. Conclusion There has been a revolution in the treatment of urge incontinence. With the introduction of tolterodine and oxybutynin XL, we now have 2 new excellent drugs with significantly less side effects. In addition, the minimally invasive surgical technique of SNS gives urologists a new procedure to treat patients with refractory conditions. Lastly, the investigative technique of instilling intravesical resiniferatoxin promises target-specific and long-lasting therapy in the future. References 1. McGuire EJ, Lytton B, Kohorn EI, Pepe V: The value of urodynamic testing in stress urinary incontinence. J Urol 124(2):256-258, 1980. 2. McGuire EJ, Lytton B: Pubovaginal sling procedure for stress incontinence. J Urol 119(1):8284, 1978. 3. Chancellor MB, Blaivas JG: Diagnostic evaluation of incontinence in patients with neurological disorders. Comp Ther 17(2):37-43, 1991. 4. Nitti VW, Raz S: Obstruction following antiincontinence procedures: diagnosis and treatment with transvaginal urethrolysis: J Urol 152(1):93-98, 1994. 5. Appell RA: Clinical efficacy and safety of tolterodine in the treatment of overactive bladder: a pooled analysis. Urology 50 (suppl 6A): 90-96, 1997. 6. Abrams P, Freeman R, Anderstrom C, Mattiasson A: Tolterodine, a new antimuscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder. Br J Urol: 81(6):801-810, 1998. 7. Van Kerrebroeck PE, Amarenco G, Thuroff JW, et al: Dose-ranging study of tolterodine in patients with detrusor hyperreflexia. Neurourol Urodynam 17(5):499-512,1998. 8. Moore KH, Sutherst JR: Response to treatment of detrusor instability in relation to psychoneurotic status. Br J Urol 66(5):486-490, 1990. 9. Gupka SK, Sathyan G: Pharmacokinetics of an oral once-a-day controlled-release oxybutynin formulation compared with immediate-release oxybutynin. J Clin Pharmacol 39(3):289-296, 1999. 10. Briggs RS, Castleden CM, Asher MJ: The effect of flavoxate on uninhibited detrusor contractions and urinary incontinence in the elderly. J Urol 123(5):665-666, 1980. 11. Chapple CR, Parkhouse H, Gardener C, Milroy EJ: Double-blind, placebo-controlled, crossover study of flavoxate in the treatment of idiopathic detrusor instability. Br J Urol 66(5):491494, 1990. SPRING 1999 REVIEWS IN UROLOGY 119